Genetic Loss of LCK Kinase Leads to Acceleration of Chronic Lymphocytic Leukemia.
Animals
B-Lymphocytes
/ metabolism
Biomarkers, Tumor
Disease Models, Animal
Disease Progression
Disease Susceptibility
Gene Deletion
Immunophenotyping
Leukemia, Lymphocytic, Chronic, B-Cell
/ genetics
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
/ deficiency
Mice
Mice, Knockout
Phenotype
Receptors, Antigen, B-Cell
/ genetics
BCR
CLL
LCK
NFAT2
NFATc1
Richter's transformation
anergy
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2020
2020
Historique:
received:
14
04
2020
accepted:
23
07
2020
entrez:
28
9
2020
pubmed:
29
9
2020
medline:
1
5
2021
Statut:
epublish
Résumé
Most patients with chronic lymphocytic leukemia (CLL) exhibit an indolent disease course and unresponsive B cell receptors (BCRs) exemplified by an anergic phenotype of their leukemic cells. In up to 5% of patients, CLL transforms from an indolent subtype to an aggressive form of B cell lymphoma (Richter's syndrome), which is associated with worse disease outcome and severe downregulation of NFAT2. Here we show that ablation of the tyrosine kinase LCK, which has previously been characterized as a main NFAT2 target gene in CLL, leads to loss of the anergic phenotype, thereby restoring BCR signaling, which results in an acceleration of CLL. Our study identifies LCK as a main player in mediating BCR unresponsiveness and its role as a crucial regulator of anergy in CLL.
Identifiants
pubmed: 32983140
doi: 10.3389/fimmu.2020.01995
pmc: PMC7492521
doi:
Substances chimiques
Biomarkers, Tumor
0
Receptors, Antigen, B-Cell
0
LCK protein, human
EC 2.7.10.2
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
EC 2.7.10.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1995Informations de copyright
Copyright © 2020 Märklin, Fuchs, Tandler, Heitmann, Salih, Kauer, Quintanilla-Martinez, Wirths, Kopp and Müller.
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